title: Silencing IL-23 expression by a small hairpin RNA protects against asthma in mice.
abstract: To determine the impact of IL-23 knockdown by RNA interference on the development and severity of ovalbumin (OVA)-induced asthmatic inflammation, and the potential mechanisms in mice, the IL-23-specific RNAi-expressing pSRZsi-IL-23p19 plasmid was constructed and inhaled into OVA-sensitized mice before each challenge, as compared with that of control mice treated with alum or budesonide. Inhalation of the pSRZsi-IL-23p19, significantly reduced the levels of OVA-challenge induced IL-23 in the lung tissues by nearly 75%, determined by RT-PCR. In addition, knockdown of IL-23 expression dramatically reduced the numbers of eosinophils and neutrophils in BALF and mitigated inflammation in the lungs of asthmatic mice. Furthermore, knockdown of IL-23 expression significantly decreased the levels of serum IgE, IL-23, IL-17, and IL-4, but not IFNgamma, and its anti-inflammatory effects were similar to or better than that of treatment with budesonide in asthmatic mice. Our data support the notion that IL-23 and associated Th17 responses contribute to the pathogenic process of bronchial asthma. Knockdown of IL-23 by RNAi effectively inhibits asthmatic inflammation, which is associated with mitigating the production of IL-17 and IL-4 in asthmatic mice.
authors.affiliation: Department of Pediatrics, The First Hospital of Jilin University, Changchun, Jilin, China.
authors.forename: Yanchun
authors.initials: Y
authors.lastname: Li
authors.forename: Meng
authors.initials: M
authors.lastname: Sun
authors.forename: Huanji
authors.initials: H
authors.lastname: Cheng
authors.forename: Shanyu
authors.initials: S
authors.lastname: Li
authors.forename: Li
authors.initials: L
authors.lastname: Liu
authors.forename: Hongmei
authors.initials: H
authors.lastname: Qiao
authors.forename: Shucheng
authors.initials: S
authors.lastname: Hua
authors.forename: Jirong
authors.initials: J
authors.lastname: Lu
mesh_terms: D000818:Animals; D001249:Asthma / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D004797:Enzyme-Linked Immunosorbent Assay; D004804:Eosinophils; D005260:Female; D007249:Inflammation / Q000378:metabolism; D053759:Interleukin-23 / Q000235:genetics*; D007958:Leukocyte Count; D051379:Mice; D008807:Mice, Inbred BALB C; D009504:Neutrophils; D010047:Ovalbumin / Q000494:pharmacology; D010957:Plasmids / Q000235:genetics; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D058504:Th17 Cells / Q000276:immunology
chemical_list: D053759:Interleukin-23; D034741:RNA, Small Interfering; D010047:Ovalbumin